MECHANISMS OF DISEASE PATHOLOGY: AN IN-VITRO INVESTIGATION OF PULMONARY FIBROBLASTS IN IDIOPATHIC PULMONARY FIBROSIS
Date
2019
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Abstract
Idiopathic pulmonary fibrosis (IPF) is a poorly understood fibrotic disease that claims the lives of more than 40,000 Americans every year. The current pathological model of IPF describes an observed significant increase in the number of pulmonary fibroblasts, increased interstitial wall thickening, and abnormal deposition of extracellular matrix terminating in severe distortion of lung architecture. To explore the various disease pathways in IPF, our lab isolates the fibroblast from donor patients using two primary methodologies, explant outgrowth, and differential binding. In this work, we demonstrate that removing the IPF fibroblast from the disease environment changes the behavior and activity of the fibroblast. We show that the methodology used to isolate these fibroblasts has a dramatic effect on the phenotype of the fibroblast. To accomplish this, we profiled the transcriptome of the fibroblast at different stages of isolation, directly after isolation and three weeks later. In addition to enumerating the pathways that are altered, we explore some of these pathways to identify a target for therapy. Finally, we ask if there are long term changes to the epigenetic regulation of the identified pathways that may have on impact on how the cell responds to challenge. This work sheds important light on the choices that researchers make in the isolation of fibroblasts and proposes the application of multiple isolation techniques in the study of IPF pathology.